Diarrhea remains an important problem for HIV-infected subjects in the highly active antiretroviral therapy (HAART) era, impacting negatively on quality of life, despite the extensive use of anti-diarrheals. Causes are many and include HIV enteropathy, overgrowth of unusual microbial agents, common enteric pathogens malignancy, and adverse effects of HAART therapy itself (Kartalija 1999).
While definitions and methods of reporting vary, it is estimated that around half of all HIV-AIDS subjects will have diarrhea at some point during their illness. Although the incidence of diarrhea did not change during the introduction of HAART, the etiologies of diarrhea changed significantly with an increase of noninfectious causes and a decrease in opportunistic infectious causes.
Managing diarrhea will assist in improving overall efficacy of anti-viral drug therapies, as well as quality of life, and controlling weight loss in HIV-positive subjects. Diarrhea may result in reduced antiretroviral compliance and/or necessitate switching ARV regimens. Diarrhea has also been associated with reduced antiretroviral drug levels, suggesting that adequate treatment will improve the absorption of ARV medication. On a population-wide basis, adherence to drug treatment regimens and maintenance of adequate ARV levels are important for minimizing the development of drug resistant strains of the virus. Therefore, drug-related diarrhea in HIV-positive subjects represents an important and unmet clinical need requiring more effective management. Currently prescribed therapies are only partially effective or are plagued by unacceptable side effects such as constipation and the potential for addiction. The development of a drug for the treatment of HIV-associated diarrhea with a low potential for drug-drug interactions, effects on drug metabolism, or abuse potential would provide an important benefit for HIV-infected subjects.